细胞毒性T细胞
癌症研究
T细胞受体
免疫系统
免疫学
细胞毒性
生物
T细胞
宫颈癌
抗原
人类白细胞抗原
诱导多能干细胞
癌症
基因
胚胎干细胞
体外
生物化学
遗传学
作者
Yasushi Furukawa,Midori Ishii,Jun Ando,Kazuya Ikeda,Kyomi J. Igarashi,Shintaro Kinoshita,Yoko Azusawa,Tokuko Toyota,Takeshi Honda,Mahito Nakanishi,Koichi Ohshima,Azuchi Masuda,Emiko Yoshida,Mari Kitade,Matthew H. Porteus,Yasuhisa Terao,Hiromitsu Nakauchi,Miki Ando
标识
DOI:10.1016/j.xcrm.2023.101327
摘要
Functionally rejuvenated human papilloma virus-specific cytotoxic T lymphocytes (HPV-rejTs) generated from induced pluripotent stem cells robustly suppress cervical cancer. However, autologous rejT generation is time consuming, leading to difficulty in treating patients with advanced cancer. Although use of allogeneic HPV-rejTs can obviate this, the major obstacle is rejection by the patient immune system. To overcome this, we develop HLA-A24&-E dual integrated HPV-rejTs after erasing HLA class I antigens. These rejTs effectively suppress recipient immune rejection while maintaining more robust cytotoxicity than original cytotoxic T lymphocytes. Single-cell RNA sequencing performed to gain deeper insights reveal that HPV-rejTs are highly enriched with tissue resident memory T cells, which enhance cytotoxicity against cervical cancer through TGFβR signaling, with increased CD103 expression. Genes associated with the immunological synapse also are upregulated, suggesting that these features promote stronger activation of T cell receptor (TCR) and increased TCR-mediated target cell death. We believe that our work will contribute to feasible “off-the-shelf” T cell therapy with robust anti-cervical cancer effects.
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